Apoproteins regulate specific metabolic functions of the lipoproteins. ApoA-IV, an apoprotein synthesized by the intestine of human and rat and incorporated onto chylomicrons before secretion, has not been assigned a function in lipid metabolism. During lipolysis by lipoprotein lipase action upon chylomicrons to form chylomicron remnants in rats, an atherosclerosis-resistant animal model, apoA-IV is transferred to circulating HDL. Chylomicron lipolysis in man causes similar dissociation of apoA-IV but, in contrast, the dissociated apoprotein does not reassociate with any of the circulating lipoproteins but instead remains free in the plasma. This project proposes to determine why apoA-IV remains associated with lipoproteins in the rat but not in man, whether this difference in association relates to the development of atherosclerosis, whether a specific receptor that recognizes apoA-IV exists and whether apoA-IV modulates binding of chylomicron remnants to the hepatic apoE receptor and binding of HDL to hepatocytes. Specific aims: a. Isolation of apoA-IV from rat and human plasma. b. Preparation of monoclonal antibodies to apoA-IV. c. Study of the solution properties of apoA-IV by physical methods. d. Determination of lipid-binding properties of apoA-IV to phospholipids and to triglyceride-rich model lipoproteins. e. Comparison of binding and catabolism of apoA-IV/lipid complexes to mixed apoA-IV, apoE/lipid complexes and mixed apoA-IV, apoA-1/lipid complexes in intact rats, perfused livers and in cultured rat hepatocytes. f. Determination of apoA-IV regulation upon binding and metabolism of chylomicron remnants and HDL. Potential significance of this research includes determining the unknown function of apoA-IV in lipid metabolism and the specific role of apoA-IV in the processing of triglyceride-rich lipoproteins formed in response to our daily dietary intake of cholesterol and fats which, in excess, enhances the potential for development of atheroscleros.